Prostate Cancer
Conditions
Brief summary
This study is a large observational study, set-up to observe how long-term treatment with FIRMAGON (hormone regulator) compare to other treatments in regards to cardiovascular events, changes in bone density, changes in blood sugar levels or liver enzyme levels in subjects with prostate cancer. Subjects will be treated according to their routine clinical care and not dictated by the study. As the study is observational in nature, the study will collect data relating to the events specified above. Subjects that agree to this study will be followed-up for 5 years. Subject data will be collected every 3 months for the first 2 years and every 6 months for the last 3 years.
Interventions
None listed
Sponsors
Ferring Pharmaceuticals
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
* Diagnosed with prostate cancer and indicated for androgen deprivation therapy (ADT) * Decision made to prescribe ADT prior to enrolment * Willing and able to provide written informed consent
Exclusion criteria
* Participation in an interventional clinical study in which any treatment or follow-up is mandated * Treatment with a GnRH receptor antagonist other than FIRMAGON * Had previous or is currently under hormonal management of prostate cancer, except for subjects who have undergone therapy with curative intention where neoadjuvant/adjuvant therapy allowed for maximum 6 months. Treatment should be terminated at least 6 months prior to baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Glucose | From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study) | Change from baseline in serum glucose are presented. |
| Incidence Rate of Adverse Events of Special Interest (AESI): Cardiovascular Events | From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study) | The incidence rate (IR) expressed as number of events per 100 patient-years of exposure (PYE). |
| Incidence Rate of AESI: Decreased Bone Density | From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study) | IR of osteoporosis or osteopenia and bone fracture events are presented. The IR is expressed as number of events per 100 PYE. |
| Incidence Rate of AESI: Glucose Intolerance or Type 2 Diabetes Mellitus (T2DM) | From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study) | IR of new onset or exacerbation of glucose intolerance or T2DM were presented. The IR expressed as number of events per 100 PYE. Glucose intolerance events were defined as events of levels of fasting glucose of 6.1 to 6.9 mmol/L |
| Change in Hepatic Enzymes | From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study) | Change from baseline in hepatic enzyme levels (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], and alkaline phosphatase \[ALP\]) are presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Long Term Evaluation of Clinical Evolution of Prostate Cancer | From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study) | Change in prostate specific antigen (PSA) is presented. |
| Changes in Testosterone Levels | From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study) | Change from baseline in testosterone levels are presented. |
| All-cause of Mortality | From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study) | A summary of IRs of all-cause mortality is presented. |
| Number and Classification of New Adverse Drug Reactions (ADRs) | From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study) | An ADR was defined as an AE assessed by investigator as possibly/probably related to the investigational product. Any new potentially unrecognized ADRs were presented. |
Countries
Belgium, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Netherlands, Norway, Portugal, Slovakia, Switzerland, United Kingdom
Participant flow
Recruitment details
A total of 136 sites in 15 European countries (Belgium, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Netherlands, Norway, Portugal, Slovakia, Switzerland, United Kingdom) recruited subjects to this observational study between January 2011 to April 2013, and the last subject completed the last visit in March 2018.
Pre-assignment details
A total of 1,515 subjects were screened, of which 1,493 subjects were found to be eligible and exposed to treatment; 1,000 subjects in the FIRMAGON group and 493 subjects in the gonadotrophin releasing hormone (GnRH) agonist group.
Participants by arm
| Arm | Count |
|---|---|
| FIRMAGON FIRMAGON (Degarelix, a GnRH antagonist) was prescribed in accordance with the approved label | 1,000 |
| GnRH Agonist Any GnRH agonist prescribed in accordance with the approved labels | 493 |
| Total | 1,493 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 277 | 92 |
| Overall Study | Covers a diverse set of reasons | 234 | 92 |
| Overall Study | Lost to Follow-up | 115 | 47 |
| Overall Study | Withdrawal by Subject | 61 | 36 |
Baseline characteristics
| Characteristic | FIRMAGON | GnRH Agonist | Total |
|---|---|---|---|
| Age, Continuous Age | 71.9 years STANDARD_DEVIATION 8.33 | 73.2 years STANDARD_DEVIATION 8.27 | 72.4 years STANDARD_DEVIATION 8.33 |
| BMI (kg/m^2) | 27 kg/m^2 STANDARD_DEVIATION 3.91 | 26.8 kg/m^2 STANDARD_DEVIATION 3.82 | 26.9 kg/m^2 STANDARD_DEVIATION 3.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 5 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 697 Participants | 353 Participants | 1050 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 71 Participants | 27 Participants | 98 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 14 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 26 Participants | 8 Participants | 34 Participants |
| Race (NIH/OMB) White | 745 Participants | 360 Participants | 1105 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1000 Participants | 493 Participants | 1493 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 141 / 1,000 | 72 / 493 |
| other Total, other adverse events | 294 / 1,000 | 110 / 493 |
| serious Total, serious adverse events | 236 / 1,000 | 144 / 493 |
Outcome results
Primary
Change in Hepatic Enzymes
Change from baseline in hepatic enzyme levels (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], and alkaline phosphatase \[ALP\]) are presented.
Time frame: From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study)
Population: The safety analysis set comprised of all subjects treated with at least one dose of medicinal product. The data was restricted to main treatment period (from signing of informed consent and administration of first dose until loss to follow-up, change/discontinuation in ADT, or end-of-study visit, whatever came first).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FIRMAGON | Change in Hepatic Enzymes | ALT (Visit 6, Month 15) | -0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALT (Visit 8, Month 21) | -0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALT (Visit 12, Month 42) | -0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALT (Visit 14, Month 54) | -1.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALP (Visit 3, Month 6) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALP (Visit 11, Month 36) | -0.3 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | AST (Visit 9, Month 24) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALT (Visit 2, Month 3) | 0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALT (Visit 3, Month 6) | 0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALT (Visit 4, Month 9) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALT (Visit 5, Month 12) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALT (Visit 7, Month 18) | -0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALT (Visit 9, Month 24) | -0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALT (Visit 10, Month 30) | -0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALT (Visit 11, Month 36) | -0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALT (Visit 13, Month 48) | -1.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALT (Visit 15, end of trial [EOT], Month 60) | -0.2 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALP (Visit 2, Month 3) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALP (Visit 4, Month 9) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALP (Visit 5, Month 12) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALP (Visit 6, Month 15) | 0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALP (Visit 7, Month 18) | 0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALP (Visit 8, Month 21) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALP (Visit 9, Month 24) | 0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALP (Visit 10, Month 30) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALP (Visit 12, Month 42) | -0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALP (Visit 13, Month 48) | -0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALP (Visit 14, Month 54) | -0.2 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | ALP (Visit 15 [EOT], Month 60) | -5.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | AST (Visit 2, Month 6) | 0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | AST (Visit 3, Month 9) | 0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | AST (Visit 4, Month 12) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | AST (Visit 5, Month 15) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | AST (Visit 6, Month 15) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | AST (Visit 7, Month 18) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | AST (Visit 8, Month 21) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | AST (Visit 10, Month 30) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | AST (Visit 11, Month 36) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | AST (Visit 12, Month 40) | 0.0 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | AST (Visit 13, Month 48) | -0.1 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | AST (Visit 14, Month 54) | -0.3 IU/L |
| FIRMAGON | Change in Hepatic Enzymes | AST (Visit 15 [EOT], Month 60) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | AST (Visit 4, Month 12) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALP (Visit 7, Month 18) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | AST (Visit 13, Month 48) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALT (Visit 12, Month 42) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALT (Visit 13, Month 48) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALP (Visit 8, Month 21) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALP (Visit 2, Month 3) | -0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | AST (Visit 5, Month 15) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALP (Visit 10, Month 30) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALP (Visit 9, Month 24) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | AST (Visit 11, Month 36) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | AST (Visit 9, Month 24) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALP (Visit 11, Month 36) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALT (Visit 2, Month 3) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | AST (Visit 6, Month 15) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALT (Visit 3, Month 6) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALP (Visit 12, Month 42) | 0.2 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALT (Visit 4, Month 9) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | AST (Visit 15 [EOT], Month 60) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALT (Visit 5, Month 12) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALT (Visit 7, Month 18) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALT (Visit 6, Month 15) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALP (Visit 13, Month 48) | 0.2 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALT (Visit 8, Month 21) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | AST (Visit 7, Month 18) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALT (Visit 9, Month 24) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALP (Visit 14, Month 54) | 0.3 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALT (Visit 10, Month 30) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | AST (Visit 12, Month 40) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALT (Visit 11, Month 36) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALP (Visit 15 [EOT], Month 60) | 0.2 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALT (Visit 14, Month 54) | -0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | AST (Visit 8, Month 21) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALT (Visit 15, end of trial [EOT], Month 60) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | AST (Visit 2, Month 6) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALP (Visit 3, Month 6) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | AST (Visit 14, Month 54) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALP (Visit 4, Month 9) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | AST (Visit 3, Month 9) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALP (Visit 5, Month 12) | 0.1 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | AST (Visit 10, Month 30) | 0.0 IU/L |
| GnRH Agonist | Change in Hepatic Enzymes | ALP (Visit 6, Month 15) | 0.0 IU/L |
Primary
Change in Hepatic Enzymes
Change from baseline in hepatic enzyme level (bilirubin) is presented.
Time frame: From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study)
Population: The safety analysis set comprised of all subjects treated with at least one dose of medicinal product. The data was restricted to main treatment period (from signing of informed consent and administration of first dose until loss to follow-up, change/discontinuation in ADT, or end-of-study visit, whatever came first).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FIRMAGON | Change in Hepatic Enzymes | Visit 14, Month 54 | -1.3 umol/L |
| FIRMAGON | Change in Hepatic Enzymes | Visit 8, Month 21 | -1.5 umol/L |
| FIRMAGON | Change in Hepatic Enzymes | Visit 4, Month 9 | -0.9 umol/L |
| FIRMAGON | Change in Hepatic Enzymes | Visit 9, Month 24 | -0.8 umol/L |
| FIRMAGON | Change in Hepatic Enzymes | Visit 2, Month 3 | -1.0 umol/L |
| FIRMAGON | Change in Hepatic Enzymes | Visit 10, Month 30 | -1.4 umol/L |
| FIRMAGON | Change in Hepatic Enzymes | Visit 5, Month 12 | -1.3 umol/L |
| FIRMAGON | Change in Hepatic Enzymes | Visit 11, Month 36 | -1.8 umol/L |
| FIRMAGON | Change in Hepatic Enzymes | Visit 15 (EOT), Month 60 | -1.9 umol/L |
| FIRMAGON | Change in Hepatic Enzymes | Visit 12, Month 40 | -1.6 umol/L |
| FIRMAGON | Change in Hepatic Enzymes | Visit 6, Month 15 | -0.9 umol/L |
| FIRMAGON | Change in Hepatic Enzymes | Visit 13, Month 48 | -0.9 umol/L |
| FIRMAGON | Change in Hepatic Enzymes | Visit 3, Month 6 | -1.0 umol/L |
| FIRMAGON | Change in Hepatic Enzymes | Visit 7, Month 18 | -1.2 umol/L |
| GnRH Agonist | Change in Hepatic Enzymes | Visit 15 (EOT), Month 60 | -0.8 umol/L |
| GnRH Agonist | Change in Hepatic Enzymes | Visit 2, Month 3 | -1.0 umol/L |
| GnRH Agonist | Change in Hepatic Enzymes | Visit 3, Month 6 | -2.0 umol/L |
| GnRH Agonist | Change in Hepatic Enzymes | Visit 4, Month 9 | -0.6 umol/L |
| GnRH Agonist | Change in Hepatic Enzymes | Visit 5, Month 12 | -0.6 umol/L |
| GnRH Agonist | Change in Hepatic Enzymes | Visit 6, Month 15 | -0.7 umol/L |
| GnRH Agonist | Change in Hepatic Enzymes | Visit 7, Month 18 | -0.4 umol/L |
| GnRH Agonist | Change in Hepatic Enzymes | Visit 8, Month 21 | -1.1 umol/L |
| GnRH Agonist | Change in Hepatic Enzymes | Visit 9, Month 24 | -1.5 umol/L |
| GnRH Agonist | Change in Hepatic Enzymes | Visit 10, Month 30 | -0.4 umol/L |
| GnRH Agonist | Change in Hepatic Enzymes | Visit 11, Month 36 | -3.2 umol/L |
| GnRH Agonist | Change in Hepatic Enzymes | Visit 12, Month 40 | -1.7 umol/L |
| GnRH Agonist | Change in Hepatic Enzymes | Visit 13, Month 48 | -1.9 umol/L |
| GnRH Agonist | Change in Hepatic Enzymes | Visit 14, Month 54 | -1.9 umol/L |
Primary
Change in Serum Glucose
Change from baseline in serum glucose are presented.
Time frame: From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study)
Population: The safety analysis set comprised of all subjects treated with at least one dose of medicinal product. The data was restricted to main treatment period (from signing of informed consent and administration of first dose until loss to follow-up, change/discontinuation in ADT, or end-of-study visit, whatever came first).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FIRMAGON | Change in Serum Glucose | Visit 7, Month 18 | 0.0 mmol/L |
| FIRMAGON | Change in Serum Glucose | Visit 14, Month 54 | 0.0 mmol/L |
| FIRMAGON | Change in Serum Glucose | Visit 8, Month 21 | 0.0 mmol/L |
| FIRMAGON | Change in Serum Glucose | Visit 4, Month 9 | 0.1 mmol/L |
| FIRMAGON | Change in Serum Glucose | Visit 9, Month 24 | 0.0 mmol/L |
| FIRMAGON | Change in Serum Glucose | Visit 2, Month 3 | 0.0 mmol/L |
| FIRMAGON | Change in Serum Glucose | Visit 10, Month 30 | 0.0 mmol/L |
| FIRMAGON | Change in Serum Glucose | Visit 5, Month 12 | 0.0 mmol/L |
| FIRMAGON | Change in Serum Glucose | Visit 11, Month 36 | 0.0 mmol/L |
| FIRMAGON | Change in Serum Glucose | Visit 15 (EOT), Month 60 | 0.1 mmol/L |
| FIRMAGON | Change in Serum Glucose | Visit 12, Month 42 | 0.1 mmol/L |
| FIRMAGON | Change in Serum Glucose | Visit 6, Month 15 | 0.0 mmol/L |
| FIRMAGON | Change in Serum Glucose | Visit 13, Month 48 | 0.2 mmol/L |
| FIRMAGON | Change in Serum Glucose | Visit 3, Month 6 | 0.0 mmol/L |
| GnRH Agonist | Change in Serum Glucose | Visit 13, Month 48 | 0.0 mmol/L |
| GnRH Agonist | Change in Serum Glucose | Visit 15 (EOT), Month 60 | 0.2 mmol/L |
| GnRH Agonist | Change in Serum Glucose | Visit 2, Month 3 | 0.0 mmol/L |
| GnRH Agonist | Change in Serum Glucose | Visit 3, Month 6 | 0.0 mmol/L |
| GnRH Agonist | Change in Serum Glucose | Visit 4, Month 9 | 0.1 mmol/L |
| GnRH Agonist | Change in Serum Glucose | Visit 5, Month 12 | 0.0 mmol/L |
| GnRH Agonist | Change in Serum Glucose | Visit 6, Month 15 | 0.2 mmol/L |
| GnRH Agonist | Change in Serum Glucose | Visit 7, Month 18 | 0.2 mmol/L |
| GnRH Agonist | Change in Serum Glucose | Visit 8, Month 21 | 0.1 mmol/L |
| GnRH Agonist | Change in Serum Glucose | Visit 9, Month 24 | -0.2 mmol/L |
| GnRH Agonist | Change in Serum Glucose | Visit 10, Month 30 | 0.0 mmol/L |
| GnRH Agonist | Change in Serum Glucose | Visit 11, Month 36 | 0.2 mmol/L |
| GnRH Agonist | Change in Serum Glucose | Visit 12, Month 42 | -0.1 mmol/L |
| GnRH Agonist | Change in Serum Glucose | Visit 14, Month 54 | 0.1 mmol/L |
Primary
Incidence Rate of Adverse Events of Special Interest (AESI): Cardiovascular Events
The incidence rate (IR) expressed as number of events per 100 patient-years of exposure (PYE).
Time frame: From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study)
Population: The safety analysis set comprised of all subjects treated with at least one dose of medicinal product. The data was restricted to main treatment period (from signing of informed consent and administration of first dose until loss to follow-up, change/discontinuation in ADT, or end-of-study visit, whatever came first).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FIRMAGON | Incidence Rate of Adverse Events of Special Interest (AESI): Cardiovascular Events | 3.8 Events per 100 PYE |
| GnRH Agonist | Incidence Rate of Adverse Events of Special Interest (AESI): Cardiovascular Events | 4.5 Events per 100 PYE |
Comparison: The IRs were estimated using a Poisson-mixture regression model.p-value: 0.400795% CI: [0.536, 1.283]Wald test
Primary
Incidence Rate of AESI: Decreased Bone Density
IR of osteoporosis or osteopenia and bone fracture events are presented. The IR is expressed as number of events per 100 PYE.
Time frame: From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study)
Population: The safety analysis set comprised of all subjects treated with at least one dose of medicinal product. The data was restricted to main treatment period (from signing of informed consent and administration of first dose until loss to follow-up, change/discontinuation in ADT, or end-of-study visit, whatever came first).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FIRMAGON | Incidence Rate of AESI: Decreased Bone Density | Bone fracture | 0.3 Events per 100 PYE |
| FIRMAGON | Incidence Rate of AESI: Decreased Bone Density | Osteoporosis or Osteopenia | 1.1 Events per 100 PYE |
| GnRH Agonist | Incidence Rate of AESI: Decreased Bone Density | Bone fracture | 0.1 Events per 100 PYE |
| GnRH Agonist | Incidence Rate of AESI: Decreased Bone Density | Osteoporosis or Osteopenia | 1.4 Events per 100 PYE |
Comparison: For osteoporosis and osteopenia events. The IRs were estimated using Poisson-mixture regression model.p-value: 0.67195% CI: [0.47, 1.626]Wald test
Comparison: For bone fracture events. The IRs were estimated using Poisson-mixture regression model.p-value: 0.454495% CI: [0.367, 9.403]Wald test
Primary
Incidence Rate of AESI: Glucose Intolerance or Type 2 Diabetes Mellitus (T2DM)
IR of new onset or exacerbation of glucose intolerance or T2DM were presented. The IR expressed as number of events per 100 PYE. Glucose intolerance events were defined as events of levels of fasting glucose of 6.1 to 6.9 mmol/L
Time frame: From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study)
Population: The safety analysis set comprised of all subjects treated with at least one dose of medicinal product. The data was restricted to main treatment period (from signing of informed consent and administration of first dose until loss to follow-up, change/discontinuation in ADT, or end-of-study visit, whatever came first).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FIRMAGON | Incidence Rate of AESI: Glucose Intolerance or Type 2 Diabetes Mellitus (T2DM) | Glucose intolerance | 15.3 Events per 100 PYE |
| FIRMAGON | Incidence Rate of AESI: Glucose Intolerance or Type 2 Diabetes Mellitus (T2DM) | T2DM | 1.8 Events per 100 PYE |
| GnRH Agonist | Incidence Rate of AESI: Glucose Intolerance or Type 2 Diabetes Mellitus (T2DM) | Glucose intolerance | 13.2 Events per 100 PYE |
| GnRH Agonist | Incidence Rate of AESI: Glucose Intolerance or Type 2 Diabetes Mellitus (T2DM) | T2DM | 0.7 Events per 100 PYE |
Comparison: For glucose intolerance. The IRs were estimated using Poisson-mixture regression model.p-value: 0.252995% CI: [0.882, 1.613]Wald test
Comparison: For T2DM. The IRs were estimated using Poisson-mixture regression model.p-value: 0.020895% CI: [1.158, 5.944]Wald test
Secondary
All-cause of Mortality
A summary of IRs of all-cause mortality is presented.
Time frame: From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study)
Population: The safety analysis set comprised of all subjects treated with at least one dose of medicinal product. The data was restricted to main treatment period (from signing of informed consent and administration of first dose until loss to follow-up, change/discontinuation in ADT, or end-of-study visit, whatever came first).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FIRMAGON | All-cause of Mortality | 6.5 Events per 100 PYE |
| GnRH Agonist | All-cause of Mortality | 5.1 Events per 100 PYE |
Comparison: The analyses of all-cause mortality was based on logistic regressions.p-value: 0.082195% CI: [0.537, 1.038]Regression, Logistic
Secondary
Changes in Testosterone Levels
Change from baseline in testosterone levels are presented.
Time frame: From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study)
Population: The safety analysis set comprised of all subjects treated with at least one dose of medicinal product. The data was restricted to main treatment period (from signing of informed consent and administration of first dose until loss to follow-up, change/discontinuation in ADT, or end-of-study visit, whatever came first).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FIRMAGON | Changes in Testosterone Levels | Visit 7, Month 18 | -3.6 ng/mL |
| FIRMAGON | Changes in Testosterone Levels | Visit 15 (EOT), Month 60 | -3.870 ng/mL |
| FIRMAGON | Changes in Testosterone Levels | Visit 8, Month 21 | -3.3 ng/mL |
| FIRMAGON | Changes in Testosterone Levels | Visit 4, Month 9 | -3.6 ng/mL |
| FIRMAGON | Changes in Testosterone Levels | Visit 9, Month 24 | -3.5 ng/mL |
| FIRMAGON | Changes in Testosterone Levels | Visit 2, Month 3 | -3.6 ng/mL |
| FIRMAGON | Changes in Testosterone Levels | Visit 10, Month 30 | -3.5 ng/mL |
| FIRMAGON | Changes in Testosterone Levels | Visit 5, Month 12 | -3.6 ng/mL |
| FIRMAGON | Changes in Testosterone Levels | Visit 11, Month 36 | -3.7 ng/mL |
| FIRMAGON | Changes in Testosterone Levels | Visit 14, Month 54 | -3.380 ng/mL |
| FIRMAGON | Changes in Testosterone Levels | Visit 12, Month 42 | -3.7 ng/mL |
| FIRMAGON | Changes in Testosterone Levels | Visit 6, Month 15 | -3.5 ng/mL |
| FIRMAGON | Changes in Testosterone Levels | Visit 13, Month 48 | -3.930 ng/mL |
| FIRMAGON | Changes in Testosterone Levels | Visit 3, Month 6 | -3.8 ng/mL |
| GnRH Agonist | Changes in Testosterone Levels | Visit 15 (EOT), Month 60 | -2.2 ng/mL |
| GnRH Agonist | Changes in Testosterone Levels | Visit 14, Month 54 | -2.463 ng/mL |
| GnRH Agonist | Changes in Testosterone Levels | Visit 2, Month 3 | -3.0 ng/mL |
| GnRH Agonist | Changes in Testosterone Levels | Visit 3, Month 6 | -3.3 ng/mL |
| GnRH Agonist | Changes in Testosterone Levels | Visit 4, Month 9 | -3.190 ng/mL |
| GnRH Agonist | Changes in Testosterone Levels | Visit 5, Month 12 | -3.236 ng/mL |
| GnRH Agonist | Changes in Testosterone Levels | Visit 6, Month 15 | -3.146 ng/mL |
| GnRH Agonist | Changes in Testosterone Levels | Visit 7, Month 18 | -3.127 ng/mL |
| GnRH Agonist | Changes in Testosterone Levels | Visit 8, Month 21 | -3.175 ng/mL |
| GnRH Agonist | Changes in Testosterone Levels | Visit 9, Month 24 | -3.041 ng/mL |
| GnRH Agonist | Changes in Testosterone Levels | Visit 10, Month 30 | -2.847 ng/mL |
| GnRH Agonist | Changes in Testosterone Levels | Visit 11, Month 36 | -2.977 ng/mL |
| GnRH Agonist | Changes in Testosterone Levels | Visit 12, Month 42 | -2.835 ng/mL |
| GnRH Agonist | Changes in Testosterone Levels | Visit 13, Month 48 | -2.6 ng/mL |
Secondary
Long Term Evaluation of Clinical Evolution of Prostate Cancer
Change in prostate specific antigen (PSA) is presented.
Time frame: From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study)
Population: The safety analysis set comprised of all subjects treated with at least one dose of medicinal product. The data was restricted to main treatment period (from signing of informed consent and administration of first dose until loss to follow-up, change/discontinuation in ADT, or end-of-study visit, whatever came first).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FIRMAGON | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 2, Month 3 | -20.1 ng/mL |
| FIRMAGON | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 3, Month 6 | -19.1 ng/mL |
| FIRMAGON | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 4, Month 9 | -17.0 ng/mL |
| FIRMAGON | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 5, Month 12 | -17.5 ng/mL |
| FIRMAGON | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 6, Month 15 | -15.8 ng/mL |
| FIRMAGON | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 7, Month 18 | -16.0 ng/mL |
| FIRMAGON | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 8, Month 21 | -14.4 ng/mL |
| FIRMAGON | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 9, Month 24 | -14.0 ng/mL |
| FIRMAGON | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 10, Month 30 | -14.6 ng/mL |
| FIRMAGON | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 11, Month 36 | -15.4 ng/mL |
| FIRMAGON | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 12, Month 42 | -16.7 ng/mL |
| FIRMAGON | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 13, Month 48 | -15.1 ng/mL |
| FIRMAGON | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 14, Month 54 | -13.0 ng/mL |
| FIRMAGON | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 15 (EOT), Month 69 | -14.7 ng/mL |
| GnRH Agonist | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 12, Month 42 | -10.5 ng/mL |
| GnRH Agonist | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 2, Month 3 | -10.7 ng/mL |
| GnRH Agonist | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 9, Month 24 | -11.9 ng/mL |
| GnRH Agonist | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 3, Month 6 | -11.4 ng/mL |
| GnRH Agonist | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 14, Month 54 | -8.9 ng/mL |
| GnRH Agonist | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 4, Month 9 | -11.5 ng/mL |
| GnRH Agonist | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 10, Month 30 | -11.7 ng/mL |
| GnRH Agonist | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 5, Month 12 | -12.9 ng/mL |
| GnRH Agonist | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 13, Month 48 | -9.5 ng/mL |
| GnRH Agonist | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 6, Month 15 | -11.0 ng/mL |
| GnRH Agonist | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 11, Month 36 | -11.4 ng/mL |
| GnRH Agonist | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 7, Month 18 | -11.3 ng/mL |
| GnRH Agonist | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 15 (EOT), Month 69 | -9.0 ng/mL |
| GnRH Agonist | Long Term Evaluation of Clinical Evolution of Prostate Cancer | Visit 8, Month 21 | -11.0 ng/mL |
Secondary
Number and Classification of New Adverse Drug Reactions (ADRs)
An ADR was defined as an AE assessed by investigator as possibly/probably related to the investigational product. Any new potentially unrecognized ADRs were presented.
Time frame: From baseline upto 5 years (every 3 months from the first 2 years of the study; every 6 months for the last 3 years of the study)
Population: The safety analysis set comprised of all subjects treated with at least one dose of medicinal product. The data was restricted to main treatment period (from signing of informed consent and administration of first dose until loss to follow-up, change/discontinuation in ADT, or end-of-study visit, whatever came first).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FIRMAGON | Number and Classification of New Adverse Drug Reactions (ADRs) | 0 New ADR |
| GnRH Agonist | Number and Classification of New Adverse Drug Reactions (ADRs) | 0 New ADR |